title: Therapeutic efficacy of human embryonic stem cell-derived endothelial cells in humanized mouse models harboring a human immune system.
abstract: OBJECTIVE
  Allogeneic transplantation of human embryonic stem cell (hESC) derivatives has the potential to elicit the patient's immune response and lead to graft rejection. Although hESCs and their derivatives have been shown to have advantageous immune properties in vitro, such observations could not be determined experimentally in vivo because of ethical and technical constraints. However, the generation of humanized mice (hu-mice) harboring a human immune system has provided a tool to perform in vivo immunologic studies of human cells and tissues. Using this model, we sought to examine the therapeutic potential of hESC-derived endothelial cells, human embryonic fibroblasts, and cord blood-derived endothelial progenitor cells in a human immune system environment.
  
  
  RESULTS
  All cell types transplanted in hu-mice showed significantly reduced cell survival during the first 14 days post-transplantation compared with that observed in immunodeficient mice. During this period, no observable therapeutic effects were detected in the hindlimb ischemic mouse models. After this point, the cells demonstrated improved survival and contributed to a long-term improvement in blood perfusion. All cell types showed reduced therapeutic efficacy in hu-mice compared with NOD scid IL2 receptor gamma chain knockout mice. Interestingly, the eventual improvement in blood flow caused by the hESC-derived endothelial cells in hu-mice was not much lower than that observed in NOD scid IL2 receptor gamma chain knockout mice.
  
  
  CONCLUSIONS
  These findings suggest that hESC derivatives may be considered a good source for cell therapy and that hu-mice could be used as a preclinical in vivo animal model for the evaluation of therapeutic efficacy to predict the outcomes of human clinical trials.
authors.affiliation: From the Department of Surgery, Samsung Medical Center (H.-M.Y., S.-J.K.), and Samsung Biomedical Research Institute, Seoul, South Korea (Y.-S.C., Y.-S.L., H.-J.L.); School of Medicine, KonKuk University, Seoul, South Korea (S.-H.M., S.-J.P., H.-M.C.); and Stem Cell Research Laboratory, CHA Stem Cell Institute, CHA University, Seoul, South Korea (S.-H.M., S.-J.P., H.-M.C.).
authors.forename: Heung-Mo
authors.initials: HM
authors.lastname: Yang
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Moon
authors.forename: Young-Sil
authors.initials: YS
authors.lastname: Choi
authors.forename: Soon-Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Lee
authors.forename: Hyun-Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Chung
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002460:Cell Line; D002470:Cell Survival; D036101:Cord Blood Stem Cell Transplantation; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000276:immunology / Q000637:transplantation*; D042783:Endothelial Cells / Q000276:immunology / Q000637:transplantation*; D005312:Fetal Blood / Q000276:immunology*; D005347:Fibroblasts / Q000276:immunology / Q000637:transplantation; D006085:Graft Survival; D006614:Hindlimb; D006801:Humans; D007121:Immunocompetence; D016867:Immunocompromised Host; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D007511:Ischemia / Q000276:immunology / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic; D020127:Recovery of Function; D012039:Regional Blood Flow; D013045:Species Specificity; D013997:Time Factors; D014183:Transplantation, Heterologous
chemical_list: D015415:Biomarkers; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit
keywords: endothelial cells; hindlimb ischemia; human embryonic stem cells; humanized mouse; therapeutic efficacy